Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on May 30, 2023. Claims 2-3, 6-7, 10-11, 14, 20, 23, 27-31, 34, 42, 44-45, 55, 57 and 107 are pending and currently examined.
Claim Objection
Claim 3 is objected to for a minor abnormality:
Claim 3 misses a punctuation mark “;” and word “or” between (ii) and (iii).
Applicant is required to make proper corrections.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 23, 34 and 55 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 23 and 34 depend from canceled claims 21 and 33, respectively, while claim 55 depends from any one of claims 1-54 which include canceled claims. Therefore, it is not clear what the metes and bounds of the claims are. To facilitate examination, claims 23 and 55 are considered as being dependent from claim 2, while claim 34 is considered as being dependent from claim 31.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 2, 3, 6-7, 10, 11, 20, 23, 27-31, 34, 42, 44, 55 and 107 are rejected under 35 U.S.C. 102/103 as being unpatentable over Daugherty et al. (US 2016/0033528 A1, published on Feb. 4, 2016).
These claims are directed to a peptide display system comprising one or more display surface(s) and at least one distinct peptide(s), wherein the at least one distinct peptide comprises a binding motif selected from a motif group consisting of a number of partially random short peptides (with lengths of about 5-9 amino acid residues), and wherein the at least one distinct peptide extends from the one or more display surface(s).
Daugherty teaches an invention relating to a method for selecting and expanding polypeptide epitopes against disease-specific antibodies present in blood across a wide variety of antibody-mediated infectious and autoimmune diseases. In particular, high throughput selection methods are provided for selecting and expanding disease-relevant polypeptide epitopes against disease-specific antibodies present in a sample from a subject using polypeptide epitope libraries. See Abstract.
Daugherty teaches that random peptide libraries (RPLs) have been proposed as a potential source of diagnostic reagents capable of mimicking diverse biological antigens in the environment (Cortese, et al., Trends Biotechnol. 12(7):262-267 (1994); Kouzmitcheva, et al., Clin. Diagn. Lab Immunol. 8(1):150-160 (2001); and Bartoli, et al., Nat. Biotechnol. 16(11): 1068-1073 (1998)). Individual peptides identified from RPLs using patient sera have been capable of identifying patients with disease with modest accuracy (Bartoli, et al., Nat. Biotechnol. 16(11)10: 1068-1073 (1998); Osman, et al., Clin. Exp. Immunol. 121(2):248-254 (2000)). Diagnostic accuracy can be improved in some cases using panels of library-isolated peptides coupled with statistical classification algorithms (Spatola, et al., Anal Chem., 85(2):1215-22 (2013)), with the drawback of requiring multiple independent measurements. In spite of these advances, peptides identified from random libraries have exhibited insufficient diagnostic efficacy (sensitivity and specificity) to foster their clinical development (Spatola, et al., Anal. Chem., 85(2): 1215-22 (2013); Cortese, et al., Proc. Natl. A cad. Sci. USA 93(20): 11063-11067 (1996); and Zanoni, et al., PLoS Med. 3(9):e358 (2006)). See [0009].
Daugherty teaches that the method includes a first step of contacting diluted fluid specimen from disease subjects with a random peptide library, and then contacting the resulting sample with an antibody binding reporter protein. The random peptide library is displayed preferably on a bacterial cell, for example, E. coli. See [0017]. Daugherty teaches that, in a preferred embodiment, the method further includes constructing a focused peptide library from the peptide sequences (i.e., the peptides containing the core motif) identified from the random library, and repeating the steps of (i) contacting diluted pooled fluid specimen from disease subjects, (ii) identifying peptide displaying cells that bind to antibodies in disease specimen, (iii) subtracting out cells that do not bind to diluted pooled fluid specimen from control subjects, and (iv) identifying the disease-specific peptides. See [0018].
Daugherty teaches that the method described therein can employ any peptide display system known in the art. Numerous peptide display systems have been described in the art. For example, display of peptides on the surface of filamentous bacteriophage, or phage display, has proven a versatile and effective methodology for the isolation of peptide ligands binding to a diverse range of targets. Scott, et al. Science, 249( 4967):386-904 (1990); Norris, et al., Science, 285(5428):744-765 (1999); Arap, et al., Science, 279(5349):377-806 (1998); and Whaley, et al., Nature, 405(6787):665-668 (2000). Polypeptide display systems include mRNA and ribosome display, eukaryotic virus display, and bacterial and yeast cell surface display. Phage display involves the localization of peptides as terminal fusions to the coat proteins, e.g., pIII, pIIV of bacteriophage particles (Scott, et al., Science 249( 4967):386-390 (1990); and Lowman, et al., Biochem., 30( 45): 10832-10838 (1991)). Other display formats and methodologies include mRNA display, ribosome or polysome display, eukaryotic virus display, and bacterial, yeast, and mammalian cell surface display. Matthcakis, et al., PNAS USA, 91(19): 9022-9026 (1994); Wilson, et al., PNAS USA, 98(7):3750-3755 (2001); Shusta, et al. Curr. Opin. Biotech., 10(2):117-122 (1999); and Bader, et al., Nature Biotech., 15(6):553-557 (1997). See [0051].
Accordingly, teachings of Daugherty indicate that various peptide display libraries (peptide display systems) exist comprising large populations of individual distinct peptides (random peptides), and that these peptide libraries can be screened against molecules of interest in samples, such as disease-specific antibodies present in blood to identify from the libraries specific peptides that bind to the molecules of interest.
Since a peptide display library must contain a “distinct peptide” for it to be identified by screening against a molecule of interest, it is expected that peptide display libraries used or taught in Daugherty, which contain displayed “random peptides” (a pool of huge number of different individual “distinct peptides”), contain one or more of the partially random peptides as claimed.
Accordingly, at least one of peptide display libraries disclosed in Daugherty is expected to comprise the “at least one distinct peptide, wherein the at least one distinct peptides comprises a binding motif” as claimed, reading on the claimed “peptide display system”.
One may argue that a peptide display library may be too small to contain any of the claimed “distinct peptide”. In this case, one of skill in the art would have found it obvious to combine the different display libraries taught in Daugherty to expand the population of different distinct peptides so that the population of “random” peptides becomes large enough to contain at least one peptide specified by the population as claimed (which encompasses hundreds of thousand individua distinct peptides). Indeed, the “peptide display system” as claimed appears to have been obtained by screening a bacterial-based peptide display library against serum samples (possibly from subjects with SARS-CoV-2 infection). See Example in the instant Specification.
Accordingly, Daugherty anticipates or makes obvious claims 2, 3, 6-7, 10, 11, 20, 23, 27-31, 34, 42, 44, 55 and 107.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 14, 45 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Daugherty et al. (US 2016/0033528 A1, published on Feb. 4, 2016), as applied above, and Liu et al. (The Journal of Infectious Diseases 2004; 190: 797–809), in view of Poh et al. (Nat Commun 11, 2806 (2020); published online Jun. 1, 2020).
Claims 14 and 45 are directed to the peptide display system of claim 2, further specifying a single surface that is a peptide microarray, a multi-well plate, or a lateral flow assay (claim 14), or, a non-random library that is biased to represent a SARS-CoV-2 infection (claim 45).
Claim 57 is directed to a method of determining the presence of specimen antibodies specific for SARS-CoV-2 in a biological sample comprising: contacting the display system of claim 2 with a biological sample, wherein the biological sample comprises a plurality of antibodies, wherein the plurality of antibodies is known or suspected to comprise specimen antibodies specific for SARS- 12CoV-2, and wherein the contacting is under conditions sufficient for the specimen antibodies specific for SARS-CoV-2 to bind a cognate epitope; measuring the binding between the at least one distinct peptide and the specimen antibodies; and determining specimen antibodies specific for SARS-CoV-2 are present in the biological sample when binding between at least one of the at least one distinct peptides and the specimen antibodies is detected.
Relevance of Daugherty is set forth in the 102/103 rejection above. Briefly, Daugherty teaches the practice of screening random peptide libraries against blood samples from subjects of various disease conditions, including infectious diseases. See discussions above. This practice is expected to generate populations of peptides with bias towards molecules specific to the samples, e.g., disease-specific antibodies in the blood samples. However, Daugherty is silent on screening peptide display libraries against a sample from a subject with SARS-CoV-2 to generate peptides or population of peptides biased towards molecules associated with SARS-CoV-2 infection.
Liu teaches that severe acute respiratory syndrome (SARS) has emerged as a highly contagious, sometimes fatal disease. To find disease-specific B cell epitopes, phage-displayed random peptide libraries were panned on serum immunoglobulin (Ig) G antibodies from patients with SARS. Forty-nine immunopositive phage clones that bound specifically to serum from patients with SARS were selected. These phageborne peptides had 4 consensus motifs, of which 2 corresponded to amino acid sequences reported for SARS-associated coronavirus (SARSCoV). Synthetic peptide binding and competitive-inhibition assays further confirmed that patients with SARS generated antibodies against SARS-CoV. Immunopositive phage clones and epitope-based peptide antigens demonstrated clinical diagnostic potential by reacting with serum from patients with SARS. This epitope-based serologic test may be useful in laboratory detection of the virus and in further study of the pathogenesis of SARS. See Abstract.
Poh teaches that in this study, using pools of overlapping linear B-cell peptides, the authors report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralization capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus. See Abstract.
In summary, Liu teaches the practice of screening a random peptide display library against serum antibodies from patients with SARS (SARS-CoV, closely related to SARS-CoV-2) to generate peptides with SARS-associated binding activities for use in diagnosis of SARS infections. Poh teaches a study on identifying immunodominant peptides from SARS-CoV-2 spike (S) protein that strongly react to serum antibodies from subjects of SARS-CoV-2 by screening a specific SARS-CoV-2 S-derived peptide library against serum antibodies from subjects with SARS-CoV-2. Even though Poh does not use a random peptide display library, its teachings indicate that SARS-CoV-2 infection exists at the time of invention and there is a need for identifying peptides with binding activities against serum samples from subjects with the virus infection.
It would have been prima facie obvious for one of ordinary skill in the art before the filing date of the current invention to combine the teachings of Daugherty, Liu and Poh to arrive at the invention as claimed. One would have been motivated to do so to apply the random peptide display libraries used and/or taught in Daugherty and Liu in screening studies against serum samples from subjects with SARS-CoV-2 infection, taught in Poh, to identify peptides with binding activities associated with SARS-CoV-2 infection.
Regarding claim 14, all three cited references teach ELISA assays using peptides identified from screening processes. See e.g., claim 14 of Daugherty, Figure 1 of Liu, and Fig 3 of Poh. ELISA assays inherently comprise using multi-well plates.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JANET ANDRES, on (571) 272-0867, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671